The ability to respond immunologically to antigens of restricted structural heterogeneity is under autosomal dominant genetic control. In several mammalian species these immune response genes are linked to the genes controlling the major histocompatiblity antigens. In guinea pigs we have been using an in vitro system to study the functional relationship between histocompatibility antigens and the ability to make specific immune responses. Using alloantisera containing antibodies directed at the major histocompatibility antigens, we have been able to specifically suppress immune responses controlled by IR genes linked to the genes coding for those histocompatibility antigens. Recent studies have suggested that this specific immunosuppression is due to a local alteration in the lymphocyte membrane preventing the triggering of those cells by antigen. Current studies are directed at further defining the mechanisms through which antihistocompatibility reagents can produce specific immunosuppression. Information derived from these studies may lead to the development of a technology for specifically suppressing undesirable immune responses without interferring with other immune functions. This could potentially provide a means of treating or preventing some immune mediated diseases.